Research work is being carried out on various aspects of acute toxic liver injury. One line of work centers on mechanisms through which an initially localized lipid peroxidation can act at distant sites. We have shown that microsomal lipid peroxidation yields a toxigenic product (or products) which survives physical separation by filtration, from the peroxidizing microsomes. The possibility that such a filterable toxigenic product is a free radical is exceedingly remote. The toxigenic factor induced pre-lytic damage to rat red blood cells. Work will be directed toward concentration, isolation, and chemical identification of the toxigenic principle. Effects on other biological test systems will also be studied. Another line of work is concerned with the consequences of the acutely failing liver to the animal as a whole. In particular, the toxicological properties of methanethiol are being studied. This toxic product of metabolism has been implicated in hepatic coma. We are studying its inhibitory effects on various enzyme systems, and we are devising methods for detection of small quantitites of methanethiol in blood and other body fluids.